Beta-lactoglobulin (.beta.-Lg) is the most abundant whey protein in bovine milk. .beta.-Lg represents up to 50% of whey proteins in the milks of ruminants and some nonruminants such as horses, pigs, dogs, dolphins, kangaroos, cats, and whales, but is absent from the milks from humans, rodents and lagomorphs. Perez and Calvo, (1995) J. Dairy Sci. 78, 978. .beta.-Lg is a 162 amino acid polypeptide with five cysteine residues, four of which participate in intramolecular disulfide bonds. There are two major .beta.-Lg variants, designated .beta.-Lg A and .beta.-Lg B, which differ at two amino acid positions. Swaisgood, (1982) Developments in Dairy Chemistry 1, 1-59 (Fox, P. F., ed.), Applied Science Publishers, London.
In the ruminant, .beta.-Lg primarily exists as a dimer, but is present as an 18,000 Da monomer in the milk of pigs, horses and donkeys. Perez and Calvo, (1995) J. Dairy Sci. 78, 978. Self-association to form dimers is affected by pH. Chen et al., (1993) J. Protein Chem. 12, 613. Alterations in the pH have also been reported to promote tetramerization of .beta.-Lg to form an octomer. Kumosinski and Timasheff, (1966) J. Am. Chem. Soc. 88, 5635.
Analysis of the crystal structure of .beta.-Lg indicates that the core of the molecule contains eight strands of .beta.-sheets, which form an anti-parallel .beta.-barrel (i.e., a calyx), with an .alpha.-helix and another .beta.-strand on the surface of the protein. Monaco et al., (1987) J. Mol. Biol. 197, 695. The interior of the calyx is hydrophobic. The three-dimensional structure of .beta.-Lg is very similar to that of retinol-binding protein (RBP), the primary transporter of retinol in serum, although there is only a 25-30% homology in amino acid sequence between these two proteins. Godovac-Zimmermann, (1988) TBS 13, 64.